3-phenoxybenzothioamide

• 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: 3-phenoxybenzothioamide
• 英文别名: 3-Phenoxythiobenzamide；3-phenoxybenzenecarbothioamide
• 化学式: C₁₃H₁₁NOS
• mdl: MFCD04973320
• 分子量: 229.302
• InChiKey: QJBRRYKDCBBKTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-phenoxybenzothioamide 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 作用下， 以 四氯化碳 、 乙醇 为溶剂， 生成 ethyl 4-(bromomethyl)-2-(3-phenoxyphenyl)thiazole-5-carboxylate
  参考文献：
  名称：

  通过De Novo Evoluton，合成，生物学评估和分子动力学模拟鉴定蛋白酪氨酸磷酸酶1B（PTP1B）抑制剂。

  摘要：

  蛋白质酪氨酸磷酸酶1B（PTP1B）是一种广泛表达的50 kDa酶，也是第一个从人胎盘组织中纯化的细胞内PTP。已证明蛋白酪氨酸磷酸酶1B在胰岛素信号通路的负调控中起着重要作用，而PTP1B的过表达可能导致胰岛素抵抗的降低。因此，PTP1B已经成为治疗2型糖尿病的一种新的有希望的治疗靶标。计算机辅助药物设计（CADD），化学合成和生物活性测定导致鉴定出一种新型有效的PTP1B抑制剂化合物1a，其IC50值为4.46μM。最后，分子动力学模拟分析为化合物1a的良好活性提供了理论依据。

  DOI：

  10.1016/j.bbrc.2020.03.075

文献信息

• [EN] ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH<br/>[FR] INHIBITEURS DE ASH1L ET MÉTHODES DE TRAITEMENT AU MOYEN DE CEUX-CI
  申请人：UNIV MICHIGAN REGENTS

  公开号：WO2017197240A1

  公开（公告）日：2017-11-16

  Provided herein are small molecule inhibitors of ASH1L activity and small molecules that facilitate ASH1L degradation and methods of use thereof for the treatment of disease, including acute leukemia, solid cancers and other diseases dependent on activity of ASH1L.

  本文提供了ASH1L活性的小分子抑制剂，促进ASH1L降解的小分子以及它们的使用方法，用于治疗疾病，包括急性白血病、实体肿瘤和其他依赖于ASH1L活性的疾病。
• Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class I HDAC Enzymes and Cancer Cell Proliferation
  作者：Jiahui Tng、Junxian Lim、Kai-Chen Wu、Andrew J. Lucke、Weijun Xu、Robert C. Reid、David P. Fairlie

  DOI：10.1021/acs.jmedchem.0c00230

  日期：2020.6.11

  active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e

  在多发性骨髓瘤，白血病和淋巴瘤的临床试验中，AR-42是组蛋白脱乙酰基酶（HDAC）的口服活性抑制剂。它几乎没有氢键供体和受体，但是是手性的2-芳基丁酸酯，可能易于消旋。我们报道了非手性AR-42类似物，其包含通过季碳原子连接的环烷基，对人类I类HDAC的效力提高了40倍（例如，JT86，IC 500.7 nM，HDAC1），对五种人类癌细胞系的细胞毒性增加了25倍，而对正常人类细胞的毒性降低了多达70倍。JT86在促进MM96L黑色素瘤细胞中乙酰化组蛋白H4积累方面比racAR-42强9倍。分子模型和结构-活性之间的关系支持四氢吡喃与HDAC1的结合，而四氢吡喃则是对酶表面水的疏水屏蔽。这种有效的I类HDAC抑制剂可在AR-42活跃的疾病（癌症，寄生虫感染，炎性疾病）中显示出益处。
• Identification of protein tyrosine phosphatase 1B (PTP1B) inhibitors through De Novo Evoluton, synthesis, biological evaluation and molecular dynamics simulation
  作者：Jingwei Wu、Yangchun Ma、Hui Zhou、Liang Zhou、Shan Du、Yingzhan Sun、Weiya Li、Weili Dong、Runling Wang

  DOI：10.1016/j.bbrc.2020.03.075

  日期：2020.5

  Protein tyrosine phosphatase 1B (PTP1B) is a widely expressed 50 kDa enzyme and the first intracellular PTP to be purified from human placental tissue. It has been proved that protein tyrosine phosphatase 1B played a significant role in the negative regulation of insulin signaling pathway and overexpression of PTP1B could lead to the decrease of insulin resistance. Therefore PTP1B has emerged as a

  蛋白质酪氨酸磷酸酶1B（PTP1B）是一种广泛表达的50 kDa酶，也是第一个从人胎盘组织中纯化的细胞内PTP。已证明蛋白酪氨酸磷酸酶1B在胰岛素信号通路的负调控中起着重要作用，而PTP1B的过表达可能导致胰岛素抵抗的降低。因此，PTP1B已经成为治疗2型糖尿病的一种新的有希望的治疗靶标。计算机辅助药物设计（CADD），化学合成和生物活性测定导致鉴定出一种新型有效的PTP1B抑制剂化合物1a，其IC50值为4.46μM。最后，分子动力学模拟分析为化合物1a的良好活性提供了理论依据。
• ASH1L INHIBITORS AND METHODS OF TREATMENT THEREWITH
  申请人：The Regents of The University of Michigan

  公开号：EP3454945B1

  公开（公告）日：2022-01-19
• Design, synthesis, biological evaluation, common feature pharmacophore model and molecular dynamics simulation studies of ethyl 4-(phenoxymethyl)-2-phenylthiazole-5-carboxylate as Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) inhibitors
  作者：Jingwei Wu、Weiya Li、Zhihui Zheng、Xinhua Lu、Huan Zhang、Ying Ma、Runling Wang

  DOI：10.1080/07391102.2020.1726817

  日期：2021.3.4

  SHP2 is a non-receptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell death pathway (PD-1/PD-L1) and cell growth and differentiation pathway (MAPK). Moreover, mutations in SHP2 have been implicated in Leopard syndrome (LS), Noonan syndrome (NS), juvenile myelomonocytic leukemia (JMML) and several types of cancer and solid tumors. Thus, SHP2 inhibitors are much needed reagents for evaluation of SHP2 as a therapeutic target. A series of novel ethyl 4-(phenoxymethyl)-2-phenylthiazole-5-carboxylate derivatives were designed and synthesized, and their SHP2 inhibitory activities (IC50) were determined. Among the desired compounds, 1d shares the highest inhibitory activity (IC50 = 0.99 mu M) against SHP2. Additionally, a common feature pharmacophore model was established to explain the structure activity relationship of the desired compounds. Finally, molecular dynamics simulation was carried out to explore the most likely binding mode of compound 1d with SHP2. In brief, the findings reported here may at least provide a new strategy or useful insights in discovering novel effective SHP2 inhibitors. Communicated by Ramaswamy H. Sarma