2-苄基氨基噻唑-4-酮 | 17385-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-苄基氨基噻唑-4-酮
• 英文名称: 2-(benzylimino)thiazolidin-4-one
• 英文别名: 2-Benzylamino-thiazol-4-one；2-benzylimino-1,3-thiazolidin-4-one
• CAS: 17385-69-2
• 化学式: C₁₀H₁₀N₂OS
• mdl: MFCD03152772
• 分子量: 206.268
• InChiKey: LNJWFHNUQPUHON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-吲哚甲醛 、 2-苄基氨基噻唑-4-酮 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 8.0h， 以80%的产率得到5-((1H-indol-3-yl)methylene)-2-(benzylimino)thiazolidin-4-one
  参考文献：
  名称：

  Discovery of certain benzyl/phenethyl thiazolidinone-indole hybrids as potential anti-proliferative agents: Synthesis, molecular modeling and tubulin polymerization inhibition study

  摘要：

  A series of certain benzyl/phenethyl thiazolidinone-indole hybrids were synthesized for the study of anti-proliferative activity against A549, NCI-H460 (lung cancer), MDA-MB-231 (breast cancer), HCT-29 and HCT-15 (colon cancer) cell lines by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). We found that compound G37 displayed highest cytotoxicity with IC50 value of 0.92 +/- 0.12 mu M towards HCT-15 cancer cell line among all the synthesized compounds. Moreover, compound G37 was also tested on normal human lung epithelial cells (L132) and was found to be safe in contrast to HCT-15 cells. The lead compound G37 showed significant G2/M phase arrest in HCT-15 cells. Additionally, compound G37 significantly inhibited tubulin polymerization with IC50, value of 2.92 +/- 0.23 mu M. Mechanistic studies such as acridine orange/ethidium bromide (AO/EB) dual staining, DAPI nuclear staining, annexinV/propidium iodide dual staining, donogenic growth inhibition assays inferred that compound G37 induced apoptotic cell death in HCT-15 cells. Moreover, loss of mitochondrial membrane potential with elevated intracellular ROS levels was observed by compound G37. These compounds bind at the active pocket of the alpha/beta-tubulin with higher number of stable hydrogen bonds, hydrophobic and arene-cation interactions confirmed by molecular modeling studies.

  DOI：

  10.1016/j.bioorg.2019.103188
• 作为产物：
  描述：

  异硫氰酸苯甲酯 在 ammonium hydroxide 、 sodium acetate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 8.0h， 生成 2-苄基氨基噻唑-4-酮
  参考文献：
  名称：

  选择性GSK-3β抑制剂5-亚苄基-2-亚氨基并噻唑烷-4-酮的设计，合成及生物学评价

  摘要：

  在这项工作中，探索了亚氨基亚硝唑胺-4-酮衍生物作为选择性GSK-3β抑制剂。进行了分子对接分析以设计一系列化合物，这些化合物是使用取代的硫脲，2-溴苯乙酮和苯甲醛合成的。在这项工作中合成的25种化合物中，针对GSK-3的体外评估导致鉴定出9种具有较低纳摩尔范围（2-85 nM）活性的化合物。此外，针对CDK-2的体外评估表明，五种化合物对GSK-3具有选择性。

  DOI：

  10.1016/j.ejmech.2016.04.075

文献信息

• THIAZOLIDINONE DERIVATIVE
  申请人：Irie Takayuki

  公开号：US20110190299A1

  公开（公告）日：2011-08-04

  An object of the present invention is to provide thiazolidinone derivatives. More specifically, an object of the present invention is to provide novel compounds having a CDC7 inhibitory action. The present invention provides thiazolidinone derivatives represented by the formula (I) The compounds of the present invention inhibit the CDC7 protein kinase activity, and suppress cell proliferation.

  本发明的目的是提供噻唑烷酮衍生物。更具体地，本发明的目的是提供具有CDC7抑制作用的新化合物。本发明提供由式(I)表示的噻唑烷酮衍生物。本发明的化合物抑制CDC7蛋白激酶活性，并抑制细胞增殖。
• Novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors: Design, synthesis, biological evaluation and molecular modelling studies
  作者：Dilep Kumar Sigalapalli、Venkatesh Pooladanda、Manasa Kadagathur、Sravanthi Devi Guggilapu、Jaya Lakshmi Uppu、Chandraiah Godugu、Nagendra Babu Bathini、Neelima D. Tangellamudi

  DOI：10.1016/j.molstruc.2020.128847

  日期：2021.2

  Abstract Here-in, we present molecular design, chemical synthesis and evaluation of novel chromenyl-based 2-iminothiazolidin-4-one derivatives as tubulin polymerization inhibitors. The newly synthesized compounds were evaluated for their in vitro cytotoxicities against A549 (lung cancer), MDA-MB-231 and BT-471 (breast cancer), HepG2 (liver cancer) and HCT-116 (colon cancer) cell lines by MTT assay

  摘要 在此，我们介绍了作为微管蛋白聚合抑制剂的新型色烯基 2-iminothiazolidin-4-one 衍生物的分子设计、化学合成和评价。通过 MTT 测定评估新合成的化合物对 A549（肺癌）、MDA-MB-231 和 BT-471（乳腺癌）、HepG2（肝癌）和 HCT-116（结肠癌）细胞系的体外细胞毒性. 在合成的化合物中，化合物12b对MDA-MB-231细胞系显示出优异的抗癌活性，IC50值为0.95±1.88 μM，并在正常人支气管上皮细胞（Beas-2B）中被证实是安全的。使用形态学观察、AO/EB 和 DAPI 染色程序观察由铅 12b 诱导的细胞凋亡。更多，通过 JC-1 染色还观察到线粒体膜去极化的剂量依赖性增加。膜联蛋白 V-FITC/PI 测定证实 12b 诱导早期细胞凋亡。此外，细胞周期分析表明，MDA-MB-231 细胞在亚 G2/M 期停滞，并抑制微管蛋白聚合，IC50
• 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。
• Synthesis and activity of quinolinyl-methylene-thiazolinones as potent and selective cyclin-dependent kinase 1 inhibitors
  作者：Shaoqing Chen、Li Chen、Nam T. Le、Chunlin Zhao、Achyutharao Sidduri、Jian Ping Lou、Christophe Michoud、Louis Portland、Nicole Jackson、Jin-Jun Liu、Fred Konzelmann、Feng Chi、Christian Tovar、Qing Xiang、Yingsi Chen、Yang Wen、Lyubomir T. Vassilev

  DOI：10.1016/j.bmcl.2007.01.081

  日期：2007.4

  A novel series of quinolinyl-methylene-thiazolinones has been identified as potent and selective cyclin-dependent kinase I (CDK1) inhibitors. Their synthesis and structure activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK1 activity in vitro, and block cell cycle progression in human tumor cell lines, suggesting a potential use as antitumor agents. (c) 2007 Elsevier Ltd. All rights reserved.
• The problem of the tautomerism of 2-iminothiazolidin-4-one and some of its derivatives
  作者：N. N. Khovratovich、I. I. Chizhevskaya

  DOI：10.1007/bf00481587

  日期：1967.7