N-(4-morpholinophenylcarbamothioyl)benzamide | 301157-20-0

• 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: N-(4-morpholinophenylcarbamothioyl)benzamide
• 英文别名: N-benzoyl-N'-(4-morpholino-phenyl)-thiourea；N-Benzoyl-N'-(4-morpholino-phenyl)-thioharnstoff；N-[(4-morpholin-4-ylphenyl)carbamothioyl]benzamide
• CAS: 301157-20-0
• 化学式: C₁₈H₁₉N₃O₂S
• 分子量: 341.434
• InChiKey: ZSOPSVVEKQFKQA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  85.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(4-morpholinophenylcarbamothioyl)benzamide 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 1-(4-morpholinophenyl)thiourea
  参考文献：
  名称：

  基于结构的药物设计和合成新型 N-Aryl-2,4-联噻唑-2-胺 CYP1B1 选择性抑制剂克服 A549 细胞的紫杉醇耐药性

  摘要：

  作为一个有前途的癌症治疗靶点，CYP1B1 在紫杉醇耐药的 A549 细胞中过表达；然而，其在耐药性中的作用仍不清楚。生物信息学分析数据表明，CYP1B1与AKT/ERK1/2和粘着斑通路密切相关，从而在紫杉醇耐药和癌症迁移/侵袭中发挥重要作用。沿着类似的思路，AhR 激动剂 7,12-二甲基苯并[ a ]蒽 (DMBA) 增强了紫杉醇抗性并促进了可能源于 CYP1B1 上调的 A549 和 H460 细胞的迁移/侵袭。此外，还设计合成了 83 种新型N -芳基-2,4-联噻唑-2-胺 CYP1B1 选择性抑制剂，以验证 CYP1B1 在紫杉醇抗性 A549 细胞中的作用。令人印象深刻的是，最有效和最具选择性的一个，即77显着抑制 AKT/ERK1/2 和 FAK/SRC 通路，从而逆转紫杉醇抗性并抑制 A549/紫杉醇细胞的迁移和侵袭。总的来说，这项研究不仅展示了 CYP1B1 在紫杉醇

  DOI：

  10.1021/acs.jmedchem.2c01306
• 作为产物：
  描述：

  4-(4-硝基苯基)吗啉 在 盐酸 、 tin 、 丙酮 作用下， 生成 N-(4-morpholinophenylcarbamothioyl)benzamide
  参考文献：
  名称：

  Wang, Scientia Sinica (English Edition), 1954, vol. 3, p. 301,303

  摘要：

  DOI：

文献信息

• Design, synthesis and biological evaluation of highly potent and selective CYP1B1 inhibitors
  作者：Haoyu Zhang、Ping Xu、Ting Wang、Shiyu Wang、Weixia Li、Jianping Mao、Jian Wang、Fengjiao Zhang、Maosheng Cheng

  DOI：10.1039/d2nj05691g

  日期：——

  activity and selectivity considering CYP1A2 is crucial for drug metabolism whereas CYP1A1 is only abundantly expressed in specific malignancies and involved in drug metabolism. In this study, a highly potent and selective CYP1B1 inhibitor C9 was obtained by structural modification, with an inhibitory activity of 2.7 nM against CYP1B1, and more than 37037 and 7407 fold selectivity over CYP1A1 and 1A2

  CYP1B1 被认为是治疗癌症的有前途的目标。然而，由于 CYP1B1/1A1/1A2 活性位点之间的密切相似性，考虑到 CYP1A2 对药物代谢至关重要，而 CYP1A1 仅在特定恶性肿瘤中大量表达并参与药物代谢，因此发现兼具活性和选择性的 CYP1B1 抑制剂具有挑战性代谢。本研究通过结构修饰获得了一种高效选择性的CYP1B1抑制剂C9 ，其对CYP1B1的抑制活性为2.7 nM，对CYP1A1和1A2的选择性分别超过37037和7407倍。此外，C9有效恢复Taxol对A549/Taxol细胞的敏感性，抑制A549/Taxol细胞迁移。分子对接和分子动力学 (MD) 模拟表明，C9在与 CYP1B1 的结合中形成了必要的相互作用，并且可以保持相对稳定。总之，C9可以作为一种有效的选择性 CYP1B1 抑制剂进行进一步研究。
• Multi-dimensional target profiling of N,4-diaryl-1,3-thiazole-2-amines as potent inhibitors of eicosanoid metabolism
  作者：Carmen B. Rödl、Dominik Vogt、Simon B.M. Kretschmer、Katja Ihlefeld、Sebastian Barzen、Astrid Brüggerhoff、Janosch Achenbach、Ewgenij Proschak、Dieter Steinhilber、Holger Stark、Bettina Hofmann

  DOI：10.1016/j.ejmech.2014.07.025

  日期：2014.9

  Eicosanoids like leukotrienes and prostaglandins play a considerable role in inflammation. Produced within the arachidonic acid (AA) cascade, these lipid mediators are involved in the pathogenesis of pain as well as acute and chronic inflammatory diseases like rheumatoid arthritis and asthma. With regard to the lipid cross-talk within the AA pathway, a promising approach for an effective anti-inflammatory therapy is the development of inhibitors targeting more than one enzyme of this cascade. Within this study, thirty N-4-diaryl-1,3-thiazole-2-amine based compounds with different substitution patterns were synthesized and tested in various cell-based assays to investigate their activity and selectivity profile concerning five key enzymes involved in eicosanoid metabolism (5-, 12-, 15-lipoxygenase (LO), cyclooxygenase-1 and -2 (COX-1/-2)). With compound 7, 2-(4-phenyl)thiazol-2-ylamino)phenol (ST-1355), a multi-target ligand targeting all tested enzymes is presented, whereas compound 9, 2-(4-(4-chlorophenyl)thiazol-2-ylamino)phenol (ST-1705), represents a potent and selective 5-LO and COX-2 inhibitor with an IC50 value of 0.9 ± 0.2 μM (5-LO) and a residual activity of 9.1 ± 1.1% at 10 μM (COX-2 product formation). The promising characteristics and the additional non-cytotoxic profile of both compounds reveal new lead structures for the treatment of eicosanoid-mediated diseases.
• COMPOSITIONS AND METHODS FOR MODULATING A KINASE
  申请人：Clevexel Pharma

  公开号：EP2718290B1

  公开（公告）日：2016-05-04
• Two-component initiator system (amine-free) with very good storage stability and particular suitability for acid systems
  申请人：Utterodt Andreas

  公开号：US20070040151A1

  公开（公告）日：2007-02-22

  A two-component initiator system having accelerators for curing polymerizable materials comprising the following components: (a) a hydroperoxide compound containing one or more hydroperoxide groups that are bound to a tertiary carbon; (b) a thiourea derivative; and (c) as accelerator, a copper compound which is soluble in the preparation is preferably free of amine and is particularly suited for polymerizable dental compositions.
• US8937065B2
  申请人：——

  公开号：US8937065B2

  公开（公告）日：2015-01-20