(Z)-5-(4-methoxybenzylidene)-2-(4-methylphenyl)thiazol-4(5H)-one | 1125863-43-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (Z)-5-(4-methoxybenzylidene)-2-(4-methylphenyl)thiazol-4(5H)-one
• 英文别名: (Z)-5-(4-methoxybenzylidene)-2-(p-methylphenyl)thiazol-4(5H)one；(Z)-5-(4-methoxybenzylidene)-2-(p-tolyl)-5H-thiazol-4-one；(Z)-5-(4-methoxybenzylidene)-2-(p-tolyl)thiazol-4(5H)-one；C06；(5Z)-5-[(4-methoxyphenyl)methylidene]-2-(4-methylphenyl)-1,3-thiazol-4-one
• CAS: 1125863-43-5
• 化学式: C₁₈H₁₅NO₂S
• 分子量: 309.389
• InChiKey: MPJWONVAQZMDCG-WJDWOHSUSA-N

物化性质

• 熔点：
  222 °C(Solv: ethanol (64-17-5))
• 沸点：
  482.7±55.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  64
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Z)-5-(4-methoxybenzylidene)-2-(4-methylphenyl)thiazol-4(5H)-one 在 吡啶 、 三溴化硼 作用下， 反应 7.0h， 生成 (Z)-4-((4-oxo-2-p-tolylthiazol-5(4H)-ylidene)methyl)phenyl morpholine-4-carboxylate
  参考文献：
  名称：

  Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy

  摘要：

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.054
• 作为产物：
  描述：

  4-甲氧基苯甲醛 、 巯基乙酸 、 对甲苯腈 在 三乙胺 作用下， 反应 12.0h， 以34%的产率得到(Z)-5-(4-methoxybenzylidene)-2-(4-methylphenyl)thiazol-4(5H)-one
  参考文献：
  名称：

  通过虚拟筛选，结构优化和生物学评估鉴定5-亚苄基-2-苯基噻唑酮类作为有效的PRMT5抑制剂

  摘要：

  蛋白质精氨酸甲基转移酶5（PRMT5）是一种表观遗传学相关的酶，已被证实是胶质母细胞瘤和壁炉细胞淋巴瘤的重要治疗靶标。在本研究中，通过基于分子对接的虚拟筛选和结构优化，鉴定了11种新颖的具有5-亚苄基-2-苯基噻唑酮骨架的PRMT5抑制剂。在酶促水平下，它们针对PRMT5的IC 50值为0.77至23μM。如预期的那样，前两个有效命中位点（5和19）显示出对MV4-11细胞的有效抗增殖活性，其EC 50值低于10μM，并降低了SmD3蛋白的细胞对称精氨酸二甲基化水平。此外5和19在细胞周期停滞和凋亡效应中证明了细胞杀伤的机制。探索了这两种化合物的可能结合方式，并通过分子动力学模拟进一步验证了它们的结合方式。还讨论了此类结构的结构-活性关系（SAR），并通过分子对接模拟进一步证明了这一关系。

  DOI：

  10.1016/j.bioorg.2018.08.021

文献信息

• 吲哚酮螺环丙烷螺-噻唑酮或螺-四氢噻唑酮 类衍生物及其制备方法和应用
  申请人：中国人民解放军第四军医大学

  公开号：CN109796471B

  公开（公告）日：2021-07-16

  本发明涉及医药技术领域，具体公开了一类吲哚酮螺环丙烷螺‑噻唑酮或螺‑四氢噻唑酮类衍生物。该类衍生物是新发现的具有全新结构的抗肿瘤化合物，该化合物的结构如通式I和II所示，具有明显抗肿瘤活性。本发明还提供了该吲哚酮螺环丙烷螺‑噻唑酮或螺‑四氢噻唑酮类衍生物的制备方法，以及其在制备抗肿瘤药物中的应用。
• A Class of 5-Benzylidene-2-phenylthiazolinones with High Potency as Direct 5-Lipoxygenase Inhibitors
  作者：Bettina Hofmann、Sebastian Barzen、Carmen B. Rödl、Andreas Kiehl、Julia Borig、Aleksandra Živković、Holger Stark、Gisbert Schneider、Dieter Steinhilber

  DOI：10.1021/jm101165z

  日期：2011.3.24

  A novel class of potent direct 5-lipoxygenase (5-LO) inhibitors bearing a thiazolinone-scaffold identified by virtual screening is presented. A range of substitutions and the importance of the 2-phenyl moiety were evaluated. This series is characterized by high potency in intact polymorphonuclear leukocytes and a cell-free system, exemplified by (Z)-2-(4-chlorophenyl)-5-(4-methoxybenzylidene)-5H-thiazol-4-one (18, IC(50) = 0.28 and 0.09 mu M). These disubstituted thiazolinones may possess potential for intervention with inflammatory and allergic diseases and certain cancer types.
• [DE] NEUE INHIBITOREN DER 5-LIPOXYGENASE UND DEREN VERWENDUNGEN<br/>[EN] NOVEL INHIBITORS OF 5-LIPOXYGENASE AND USES THEREOF<br/>[FR] NOUVEAUX INHIBITEURS DE LA 5-LIPOXYGÉNASE ET UTILISATIONS DE CEUX-CI
  申请人：UNIV JW GOETHE FRANKFURT MAIN

  公开号：WO2009027077A2

  公开（公告）日：2009-03-05

  Die vorliegende Erfindung bezieht sich auf trizyklische ThiazoIon-Verbindungen und auf Imidazopyridin-Verbindungen als neuartige und effektive Inhibitoren der 5-Lipoxygenase und deren Einfluß auf den Arachidonsäure-Stoffwechsel. Die Verbindungen sind geeignet zur Behandlung von Erkrankungen, insbesondere von Leukotrien-vermittelten Erkrankungen, wie Entzündungskrankheiten, allergischen Erkrankungen, kardiovaskulären Erkrankungen, Osteoporose, Haarausfall und weiteren.
• Development and evaluation of ST-1829 based on 5-benzylidene-2-phenylthiazolones as promising agent for anti-leukotriene therapy
  作者：Andreas P. Lill、Carmen B. Rödl、Dieter Steinhilber、Holger Stark、Bettina Hofmann

  DOI：10.1016/j.ejmech.2014.10.054

  日期：2015.1

  Different inflammatory diseases and allergic reactions are mediated by leukotrienes, which arise from the oxygenation of arachidonic acid catalyzed by 5-lipoxygenase (5-LO). One promising approach for an effective anti-leukotriene therapy is the inhibition of this key enzyme. This study presents the synthesis and development of a potent and direct 5-LO inhibitor based on the well characterized 5-benzylidene-2-phenylthiazolone C06, whose further pharmacological investigation was precluded due to its low solubility. Through optimization of C06, evaluation of structure activity relationships including profound assessment of the thiazolone core and consideration of the solubility, the 5-benzyl-2-phenyl-4-hydroxythiazoles represented by 46 (ST-1829, 5-(4-chlorobenzyl)-2-p-tolylthiazol-4-ol) were developed. Compound 46 showed an improved 5-LO inhibitory activity in cell-based (IC50 values 0.14 mu M) and cell-free assays (IC50 values 0.03 mu M) as well as a prominent enhanced solubility. Furthermore, it kept its promising inhibitory potency in the presence of blood serum, excluding excessive binding to serum proteins. These facts combined with the non-cytotoxic profile mark a major step towards an effective anti-inflammatory therapy. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Identification of 5-benzylidene-2-phenylthiazolones as potent PRMT5 inhibitors by virtual screening, structural optimization and biological evaluations
  作者：Kongkai Zhu、Hongrui Tao、Jia-Li Song、Lu Jin、Yuanyuan Zhang、Jingqiu Liu、Zhifeng Chen、Cheng-Shi Jiang、Cheng Luo、Hua Zhang

  DOI：10.1016/j.bioorg.2018.08.021

  日期：2018.12

  mantel cell lymphoma. In the present study, 11 novel PRMT5 inhibitors with 5-benzylidene-2-phenylthiazolone scaffold were identified by molecular docking-based virtual screening and structural optimization. Their IC50 values against PRMT5 at enzymatic level were ranging from 0.77 to 23 μM. As expected, the top two active hits (5 and 19) showed potent anti-proliferative activity against MV4-11 cells with

  蛋白质精氨酸甲基转移酶5（PRMT5）是一种表观遗传学相关的酶，已被证实是胶质母细胞瘤和壁炉细胞淋巴瘤的重要治疗靶标。在本研究中，通过基于分子对接的虚拟筛选和结构优化，鉴定了11种新颖的具有5-亚苄基-2-苯基噻唑酮骨架的PRMT5抑制剂。在酶促水平下，它们针对PRMT5的IC 50值为0.77至23μM。如预期的那样，前两个有效命中位点（5和19）显示出对MV4-11细胞的有效抗增殖活性，其EC 50值低于10μM，并降低了SmD3蛋白的细胞对称精氨酸二甲基化水平。此外5和19在细胞周期停滞和凋亡效应中证明了细胞杀伤的机制。探索了这两种化合物的可能结合方式，并通过分子动力学模拟进一步验证了它们的结合方式。还讨论了此类结构的结构-活性关系（SAR），并通过分子对接模拟进一步证明了这一关系。