(Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione | 1208535-06-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione
• 英文别名: (5Z)-5-[(2,4-dihydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 1208535-06-1
• 化学式: C₁₀H₇NO₄S
• 分子量: 237.236
• InChiKey: CPVBTHMWQGHRIR-BAQGIRSFSA-N

物化性质

• 熔点：
  276-278 °C
• 密度：
  1.672±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(溴甲基)-7-羟基苯并吡喃-2-酮 、 (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以62%的产率得到(Z)-5-(2,4-dihydroxybenzylidene)-3-[(7-hydroxy-2-oxo-2H-chromen-4-yl)methyl]thiazolidine-2,4-dione
  参考文献：
  名称：

  Design, Synthesis and Characterization of Some Novel 3-Coumarinyl- 5-aryliden-1,3-thiazolidine-2,4-diones and Their Antioxidant Activity

  摘要：

  在我们努力获取生物活性化合物的过程中，合成了新的3,5-二取代-1,3-噻唑烷-2,4-二酮(5a - r)。通过Knoevenagel反应从1,3-噻唑烷-2,4-二酮(2)和适当的芳香醛制备了一系列5-芳基甲基亚烯-1,3-噻唑烷-2,4-二酮(3a - r)。将3a - r与7-羟基-4-溴甲基-2-氧代-2H-咖啡因(1)进行缩合反应，得到了新颖的3-(7-羟基-2-氧代-2H-咖啡因-4-基甲基)-5-芳基亚烯-1,3-噻唑烷-2,4-二酮5a - r。化合物3a - r和5a - r被评估其抗氧化活性(DPPH自由基清除活性)。

  DOI：

  10.1515/znb-2011-0210
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 2,4-二羟基苯甲醛 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 0.5h， 以69%的产率得到(Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione
  参考文献：
  名称：

  5-苯甲酰内苯并噻唑啉-4-酮作为细菌Mur Ligases的多靶标抑制剂

  摘要：

  Mur连接酶参与细菌肽聚糖生物合成的细胞内途径，并构成了诱人的药物靶标，尽管到目前为止尚未被充分利用。合成了一系列羟基取代的5-亚苄基硫唑烷丁-4-酮，并作为Mur连接酶的抑制剂进行了测试。最有效的化合物5a 具有抗MurD-F的活性，IC 50值在2至6μm之间，使其成为有希望的Mur连接酶的多靶点抑制剂。还研究了对不同菌株的抗菌活性，对蛋白激酶的抑制活性，5a 的致突变性和遗传毒性，并进行了动力学和NMR研究。

  DOI：

  10.1002/cmdc.200900449

文献信息

• NOVEL COMPOUND HAVING SKIN-WHITENING, ANTI-OXIDIZING AND PPAR ACTIVITIES AND MEDICAL USE THEREFOR
  申请人：Chung Hae Young

  公开号：US20140023603A1

  公开（公告）日：2014-01-23

  Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.

  提供了一种具有美白皮肤、抗氧化和PPAR活性的新化合物及其医疗用途，该化合物具有美白皮肤的活性，可抑制酪氨酸酶，因此适用于用于美白皮肤的药物组合物或化妆品；具有抗氧化活性，因此适用于预防和治疗皮肤老化；具有PPAR活性，特别是PPARα和PPARγ活性，因此适用于用于预防和治疗肥胖、代谢性疾病或心血管疾病的药物组合物或保健食品。
• 5-Benzylidenethiazolidin-4-ones as Multitarget Inhibitors of Bacterial Mur Ligases
  作者：Tihomir Tomašić、Nace Zidar、Andreja Kovač、Samo Turk、Mihael Simčič、Didier Blanot、Manica Müller-Premru、Metka Filipič、Simona Golič Grdadolnik、Anamarija Zega、Marko Anderluh、Stanislav Gobec、Danijel Kikelj、Lucija Peterlin Mašič

  DOI：10.1002/cmdc.200900449

  日期：2010.2.1

  Mur ligases participate in the intracellular path of bacterial peptidoglycan biosynthesis and constitute attractive, although so far underexploited, targets for antibacterial drug discovery. A series of hydroxy‐substituted 5‐benzylidenethiazolidin‐4‐ones were synthesized and tested as inhibitors of Mur ligases. The most potent compound 5 a was active against MurD–F with IC50 values between 2 and 6 μm

  Mur连接酶参与细菌肽聚糖生物合成的细胞内途径，并构成了诱人的药物靶标，尽管到目前为止尚未被充分利用。合成了一系列羟基取代的5-亚苄基硫唑烷丁-4-酮，并作为Mur连接酶的抑制剂进行了测试。最有效的化合物5a 具有抗MurD-F的活性，IC 50值在2至6μm之间，使其成为有希望的Mur连接酶的多靶点抑制剂。还研究了对不同菌株的抗菌活性，对蛋白激酶的抑制活性，5a 的致突变性和遗传毒性，并进行了动力学和NMR研究。
• Anti-melanogenic effect of (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione, a novel tyrosinase inhibitor
  作者：So Hee Kim、Young Mi Ha、Kyoung Mi Moon、Yeon Ja Choi、Yun Jung Park、Hyoung Oh Jeong、Ki Wung Chung、Hye Jin Lee、Pusoon Chun、Hyung Ryong Moon、Hae Young Chung

  DOI：10.1007/s12272-013-0184-5

  日期：2013.10

  We synthesized (Z)-5-(2,4-dihydroxybenzylidene)thiazolidine-2,4-dione (MHY498) as a potential tyrosinase inhibitor. MHY498 potently inhibited mushroom tyrosinase activity (mean IC50 = 3.55 μM) in a dose-dependent manner. MHY498 was more potent than the well-known tyrosinase inhibitor, kojic acid (mean IC50 = 22.79 μM). When tested in B16F10 melanoma cells treated with α-melanocyte stimulating hormone (α-MSH), MHY498 inhibited murine tyrosinase activity and decreased melanin production without inducing cytotoxicity. Docking models showed that the binding affinity of MHY498 to tyrosinase was higher than that of kojic acid, and docking simulation results indicated that the tyrosinase binding moieties of MHY498 and kojic acid were similar. Western blotting showed that tyrosinase inhibition by MHY498 partly resulted from the expressional modulations of tyrosinase and its transcription factor, microphthalmia-associated transcription factor, via the cAMP–PKA–CREB pathway. These findings suggest that MHY498 could be useful as an antimelanogenic agent for the prevention and treatment of diseases associated with skin pigmentation.

  我们合成了(Z)-5-(2,4-二羟基亚苄基)噻唑烷-2,4-二酮（MHY498），作为一种潜在的酪氨酸酶抑制剂。MHY498 能以剂量依赖的方式有效抑制蘑菇酪氨酸酶的活性（平均 IC50 = 3.55 μM ）。MHY498 比著名的酪氨酸酶抑制剂曲酸（平均 IC50 = 22.79 μM）更有效。在用α-黑色素细胞刺激素（α-MSH）处理的 B16F10 黑色素瘤细胞中进行测试时，MHY498 可抑制小鼠酪氨酸酶的活性并减少黑色素的生成，但不会引起细胞毒性。对接模型显示 MHY498 与酪氨酸酶的结合亲和力高于曲酸，对接模拟结果表明 MHY498 与曲酸的酪氨酸酶结合分子相似。Western印迹显示，MHY498对酪氨酸酶的抑制作用部分是通过cAMP-PKA-CREB途径调节酪氨酸酶及其转录因子--小眼症相关转录因子的表达。这些研究结果表明，MHY498 可作为一种抗黑色素生成剂，用于预防和治疗与皮肤色素沉着有关的疾病。
• NOVEL COMPOUND HAVING SKIN-WHITENING, ANTI-OXIDIZING AND PPAR ACTIVITIES AND MEDICAL USE THEREOF
  申请人：Pusan National University Industry-University Cooperation Foundation

  公开号：US20160102065A1

  公开（公告）日：2016-04-14

  Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.

  提供了一种具有美白、抗氧化和PPAR活性的新化合物及其医疗用途。该化合物具有抑制酪氨酸酶的美白活性，因此可用于美白药物组合物或化妆品产品；具有抗氧化活性，因此可用于预防和治疗皮肤老化；具有PPAR活性，特别是PPARα和PPARγ活性，因此可用于有效预防和治疗肥胖症、代谢疾病或心血管疾病的药物组合物或保健食品。
• The inhibitory effect of a synthetic compound, (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione (MHY498), on nitric oxide-induced melanogenesis
  作者：So Hee Kim、Yeon Ja Choi、Kyoung Mi Moon、Hye Jin Lee、Youngwoo Woo、Ki Wung Chung、Yuri Jung、Sora Kim、Pusoon Chun、Youngjoo Byun、Young Mi Ha、Hyung Ryong Moon、Hae Young Chung

  DOI：10.1016/j.bmcl.2013.05.094

  日期：2013.8

  Nitric oxide (NO) and the NO/PKG signaling pathway play crucial roles in ultraviolet (UV)-induced melanogenesis, which is known to be related to the induction of tyrosinase. In an attempt to find a novel anti-melanogenic agent, we synthesized (Z)-5-(2,4-dihydroxybenzylidene) thiazolidine-2,4-dione (MHY498). The purpose of this study was to investigate the effect of MHY498 on NO levels and on the NO-mediated signaling pathway using an in vitro model of melanogenesis. MHY498 inhibited 200 mu M sodium nitroprusside (SNP, a NO donor)-induced NO generation, dose-dependently and suppressed tyrosinase activity and melanin synthesis induced by SNP in B16F10 melanoma cells. To investigate the effect of MHY498 on NO-mediated signaling pathway, guanosine cyclic 3',5'-monophosphate (cGMP) activities were measured using a cGMP EIA Kit and western blotting was performed to determine the effects of MHY498 on the gene expressions of tyrosinase and microphthalmia-associated transcription factor (MITF). The increased activity of cGMP by SNP was reduced dose-dependently by pretreatment with MHY498. Furthermore, MHY498 suppressed the expressions of tyrosinase and MITF stimulated by SNP. This study shows that enhancement of tyrosinase gene expression via the cGMP pathway is a probable primary mechanism of NO-induced melanogenesis and that the NO-mediated signaling pathway with the expression of MITF enhances melanogenesis. In addition, MHY498 was found to scavenge NO and to suppress the activity of the NO-mediated signaling pathway, and thus, to subsequently down-regulate tyrosinase expression and melanogenesis. This study suggests that MHY498 is a promising anti-melanogenic agent that targets the NO-induced cGMP signaling pathway. (C) 2013 Elsevier Ltd. All rights reserved.