(Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxoimidazolidin-4-one | 110830-17-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxoimidazolidin-4-one
• 英文别名: (5Z)-5-(1,3-benzodioxol-5-ylmethylidene)-2-sulfanylideneimidazolidin-4-one
• CAS: 110830-17-6
• 化学式: C₁₁H₈N₂O₃S
• 分子量: 248.262
• InChiKey: PKAJHHBFVYAMMP-CLTKARDFSA-N

物化性质

• 熔点：
  >260 °C
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxoimidazolidin-4-one 在 potassium carbonate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 (5Z)-2-[4-[2-[2-[2-(2-aminoethoxy)ethoxy]ethoxy]ethoxy]phenylamino]-5-(benzo[1,3]dioxol-5-ylmethylene)-3,5-dihydroimidazol-4-one
  参考文献：
  名称：

  Chemical synthesis and biological validation of immobilized protein kinase inhibitory Leucettines

  摘要：

  Leucettines, a family of marine sponge-derived 2-aminoimidazolone alkaloids, are potent inhibitors of DYRKs (dual-specificity, tyrosine phosphoiylation regulated kinases) and CLKs (cdc2-like kinases). They constitute promising pharmacological leads for the treatment of several diseases, including Alzheimer's disease and Down syndrome. In order to investigate the scope of potential targets of Leucettine L41, a representative member of the chemical class, we designed an affinity chromatography strategy based on agarose-immobilized leucettines. A synthesis protocol for the attachment of a polyethylene (3 or 4 units) linker to L41 was first established. The linker attachment site on L41 was selected on the basis of the co-crystal structure of L41 with several kinases. L41 was then covalently bound to agarose beads through the primary amine located at the end of the linker. Control, kinase inactive Leucettine was also immobilized, as well as free linker devoid of ligand. Extracts of several mouse tissues revealed a complex pattern of interacting proteins, some of which probably resulting from non-specific, hydrophobic binding, while others representing bona fide Leucettine-interacting proteins. DYRK1A and GSK-3 (glycogen synthase kinase-3) were confirmed as interacting targets by Western blotting in various mouse tissues. The Leucettine affinity chromatography resin constitutes a powerful tool to purify and identify the targets of this new promising therapeutic class of molecules. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.035
• 作为产物：
  描述：

  胡椒醇 在 哌啶 、 manganese(IV) oxide 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 36.0h， 生成 (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  [EN] USE OF HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES
  [FR] UTILISATION DE DÉRIVÉS HÉTÉROCYCLIQUES AYANT UNE ACTIVITÉ DE PROLIFÉRATION DE CARDIOMYOCYTES POUR LE TRAITEMENT DE MALADIES CARDIAQUES

  摘要：

  本文提供了利用具有心肌细胞增殖活性的杂环衍生物治疗心脏疾病的用途。具体而言，揭示了使用式(I)化合物或其药学上可接受的盐、溶剂化合物、立体异构体或前药；以及其应用。可以在说明书中找到有关式中每个基团的定义的详细信息。

  公开号：

  WO2021114315A1

文献信息

• Synthesis and biological activity of 5-aryliden-2-thiohydantoin S-aryl derivatives
  作者：Alexander V. Finko、Dmitry A. Skvortsov、Dimitri N. Laikov、Gleb M. Averochkin、Egor A. Dlin、Marina A. Kalinina、Vladimir A. Aladinskiy、Nataliya S. Vorobyeva、Andrei V. Mironov、Elena K. Beloglazkina、Nikolay V. Zyk、Yan A. Ivanenkov、Alexander G. Majouga

  DOI：10.1016/j.bioorg.2020.103900

  日期：2020.7

  complementary approaches to S-arylation of 2-thiohydantoins have been developed: copper-catalyzed cross coupling with either arylboronic acids or aryl iodides under mild conditions, or direct nucleophilic substitution in activated aryl halides. For 38 diverse compounds, reaction yields for all three methods have been determined. Selected by molecular docking, they have been tested on androgen receptor activation

  已经开发出三种新的和互补的2-硫代乙内酰脲S-芳基化方法：在温和条件下与芳基硼酸或芳基碘化物进行铜催化的交叉偶联，或在活化的芳基卤化物中进行亲核取代。对于38种不同的化合物，已确定所有三种方法的反应收率。通过分子对接进行选择，它们已经在雄激素受体激活，p53-Mdm2调节以及A549，MCF7，VA13，HEK293T，PC3，LnCAP细胞系中进行了细胞毒性测试，其中两个被证明是雄激素受体激活剂（可能是通过变构调节而来的），而另一种可以激活p53级联。希望2-硫代乙内酰脲S-芳基作为生物活性化合物值得进一步研究。
• Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation
  作者：Ming-Hua Hsu、Cheng-Ying Hsieh、Mohit Kapoor、Jui-Hsun Chang、Hsueh-Liang Chu、Tsai-Mu Cheng、Kai-Cheng Hsu、Tony Eight Lin、Fu-Yuan Tsai、Jia-Cherng Horng

  DOI：10.1016/j.bioorg.2020.103729

  日期：2020.5

  a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel

  Leucettamine B是海洋海绵Leucetta microraphis中的天然产物。其家族中的几种类似物，例如aplysinopsine和clathridine，是具有药用活性的分子，已在许多药物和保健产品中应用。然而，迄今为止，尚未研究亮氨酰胺B。在这份报告中，我们描述了使用微波反应器通过Knoevenagel缩合反应获得的新型亮丙二胺B类似物的合成。测试了25种新合成的化合物对MDA-MB-468，SW480和Mahlavu细胞系的抗癌活性。其中，基于碳硼烷的化合物（Z）-5-（苯并[d] [1,3]二氧杂-5-基亚甲基）-3-（1-氯基碳烷基）-2-硫代-噻唑烷-4- （49）和（Z）-5-（benzo [d] [1，3]二恶唑-5-基亚甲基）-3-（2-（吡咯烷-1-基）乙基）-2-硫代噻唑烷酮-4-一（31）衍生物具有最强的抗肿瘤细胞潜力。碳硼烷衍生物49对SW480细胞系（4
• Microwave-Assisted Condensation Reactions of Acetophenone Derivatives and Activated Methylene Compounds with Aldehydes Catalyzed by Boric Acid under Solvent-Free Conditions
  作者：Elodie Brun、Abdelmounaim Safer、François Carreaux、Khadidja Bourahla、Jean-Martial L'helgoua'ch、Jean-Pierre Bazureau、Jose Villalgordo

  DOI：10.3390/molecules200611617

  日期：——

  We here disclosed a new protocol for the condensation of acetophenone derivatives and active methylene compounds with aldehydes in the presence of boric acid under microwave conditions. Implementation of the reaction is simple, healthy and environmentally friendly owing to the use of a non-toxic catalyst coupled to a solvent-free procedure. A large variety of known or novel compounds have thus been

  我们在这里公开了在微波条件下在硼酸存在下苯乙酮衍生物和活性亚甲基化合物与醛缩合的新方案。由于使用了无溶剂的无毒催化剂，因此该反应的实施简单，健康且对环境友好。因此，已经制备了许多已知的或新颖的化合物，包括带有酸或碱敏感性官能团的底物。
• [EN] NOVEL HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES<br/>[FR] NOUVEAUX DÉRIVÉS HÉTÉROCYCLIQUES AYANT UNE ACTIVITÉ DE PROLIFÉRATION DE CARDIOMYOCYTES POUR LE TRAITEMENT DE MALADIES CARDIAQUES
  申请人：UNIV TONGJI

  公开号：WO2021115489A1

  公开（公告）日：2021-06-17

  Provided are novel heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, provided are the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, preparation method thereof, application thereof and pharmaceutical composition useful for treatment of heart diseases.

  提供了具有心肌细胞增殖活性的新型杂环衍生物，用于治疗心脏疾病。具体提供了式（I）的化合物或药用盐、立体异构体、溶剂合物或前药，其制备方法、应用以及用于治疗心脏疾病的药物组合物。
• Structure–Activity Relationship in the Leucettine Family of Kinase Inhibitors
  作者：Tania Tahtouh、Emilie Durieu、Benoît Villiers、Céline Bruyère、Thu Lan Nguyen、Xavier Fant、Kwang H. Ahn、Leepakshi Khurana、Emmanuel Deau、Mattias F. Lindberg、Elodie Sévère、Frédéric Miege、Didier Roche、Emmanuelle Limanton、Jean-Martial L’Helgoual’ch、Guillaume Burgy、Solène Guiheneuf、Yann Herault、Debra A. Kendall、François Carreaux、Jean-Pierre Bazureau、Laurent Meijer

  DOI：10.1021/acs.jmedchem.1c01141

  日期：2022.1.27

  2-aminoimidazolin-4-ones derived from the marine sponge alkaloid Leucettamine B, have been developed as pharmacological inhibitors of DYRKs (dual specificity, tyrosine phosphorylation regulated kinases) and CLKs (cdc2-like kinases). We report here on the synthesis and structure–activity relationship (SAR) of 68 Leucettines. Leucettines were tested on 11 purified kinases and in 5 cellular assays: (1) CLK1 pre-mRNA

  蛋白激酶 DYRK1A 与阿尔茨海默病、唐氏综合症、糖尿病、病毒感染和白血病有关。Leucettines 是一种源自海绵生物碱 Leucettamine B 的 2-氨基咪唑啉-4-ones 家族，已被开发为 DYRKs（双特异性，酪氨酸磷酸化调节激酶）和 CLKs（cdc2 样激酶）的药理学抑制剂。我们在此报告 68 种亮氨酸的合成和构效关系 (SAR)。在 11 种纯化激酶和 5 种细胞测定中测试亮氨酸：(1) CLK1 pre-mRNA 剪接，(2) Threonine-212-Tau 磷酸化，(3) 谷氨酸诱导的细胞死亡，(4) 自噬和 (5) 拮抗作用配体激活的大麻素受体 CB1。对 DYRK1A 观察到的亮西汀 SAR 与 CLK1、CLK4、DYRK1B 和 DYRK2 基本相同。DYRK3 和 CLK3 对亮氨酸不太敏感。相比之下，细胞 SAR 突出了特定激酶靶标的抑制与一