2-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio)-N-phenylacetamide | 356587-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio)-N-phenylacetamide
• 英文别名: 2-[(5-methoxy-1H-benzimidazol-2-yl)thio]-N-phenylacetamide；2-[(6-methoxy-1H-benzimidazol-2-yl)sulfanyl]-N-phenylacetamide
• CAS: 356587-72-9
• 化学式: C₁₆H₁₅N₃O₂S
• 分子量: 313.38
• InChiKey: OQPNFPCQMIHCJI-UHFFFAOYSA-N

物化性质

• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-甲氧基邻苯二胺 在 potassium carbonate 、 potassium hydroxide 作用下， 以 水 、 丙酮 为溶剂， 反应 0.25h， 生成 2-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio)-N-phenylacetamide
  参考文献：
  名称：

  通过基于结构的虚拟筛选和命中优化开发的有效，选择性和细胞活性蛋白精氨酸甲基转移酶5（PRMT5）抑制剂。

  摘要：

  PRMT5在多种细胞过程中起着重要作用，并在几种人类恶性肿瘤中被上调。此外，PRMT5已被确认为套细胞淋巴瘤的抗癌靶标。在这项研究中，我们通过执行基于结构的虚拟筛选和命中优化，发现了一种有效的选择性PRMT5抑制剂。鉴定出的化合物17（IC 50 = 0.33μM）对一组其他甲基转移酶表现出广泛的选择性。通过表面等离振子共振实验验证了17与PRMT5的直接结合，K d为0.987μM。动力学实验表明17是除底物以外的SAM竞争性抑制剂。另外17提示对MV4-11细胞具有选择性的抗增殖作用，进一步的研究表明，细胞抗肿瘤活性的机制是由于PRMT5介导的SmD3甲基化的抑制。17可能是一种有前途的先导化合物，可以进一步了解PRMT5，并可能有助于开发白血病适应症的治疗方法。

  DOI：

  10.1021/acs.jmedchem.7b00587

文献信息

• Synthesis and evaluation of novel benzimidazole derivatives as antimicrobial agents
  作者：Deepkumar Joshi、Kalpesh Parikh

  DOI：10.1007/s00044-013-0732-z

  日期：2014.3

  Benzimidazole analogs bearing electron-withdrawing as well as electron-donating substituent were synthesized to achieve bioactive molecules with significant antimicrobial property. The desired compounds were prepared by multi-step synthesis process. The formation of intermediates and their corresponding derivatives (III (1-13) ) was confirmed by spectral characterization such as H-1 NMR, C-13 NMR, mass spectra, IR, and elemental analysis. The compounds were screened for their antimicrobial properties against a broad panel of Gram-positive and Gram-negative bacteria as well as fungi. From the SAR study data, it was observed that the derivatives with electron-withdrawing functional groups were more bioactive than that with electron-donating functional groups.
• [EN] ARGININE METHYLATION INHIBITOR FOR TREATING OR PREVENTING CARDIOVASCULAR DISEASE<br/>[FR] INHIBITEUR DE MÉTHYLATION DE L'ARGININE POUR LE TRAITEMENT OU LA PRÉVENTION D'UNE MALADIE CARDIOVASCULAIRE
  申请人：THE UNIV OF HULL

  公开号：WO2018130840A1

  公开（公告）日：2018-07-19

  The invention relates to the treatment and/or prevention of cardiovascular disease, for example thromboembolic conditions, such as atherothrombotic disease. In particularly, the invention relates to an arginine methylation inhibitor ('ArgMe' inhibitor) for use in the treatment and/or prevention of cardiovascular disease such as thromboembolic conditions (for example atherothrombotic disease).
• Potent, Selective, and Cell Active Protein Arginine Methyltransferase 5 (PRMT5) Inhibitor Developed by Structure-Based Virtual Screening and Hit Optimization
  作者：Ruifeng Mao、Jingwei Shao、Kongkai Zhu、Yuanyuan Zhang、Hong Ding、Chenhua Zhang、Zhe Shi、Hualiang Jiang、Dequn Sun、Wenhu Duan、Cheng Luo

  DOI：10.1021/acs.jmedchem.7b00587

  日期：2017.7.27

  been validated as an anticancer target in mantle cell lymphoma. In this study, we found a potent and selective PRMT5 inhibitor by performing structure-based virtual screening and hit optimization. The identified compound 17 (IC50 = 0.33 μM) exhibited a broad selectivity against a panel of other methyltransferases. The direct binding of 17 to PRMT5 was validated by surface plasmon resonance experiments

  PRMT5在多种细胞过程中起着重要作用，并在几种人类恶性肿瘤中被上调。此外，PRMT5已被确认为套细胞淋巴瘤的抗癌靶标。在这项研究中，我们通过执行基于结构的虚拟筛选和命中优化，发现了一种有效的选择性PRMT5抑制剂。鉴定出的化合物17（IC 50 = 0.33μM）对一组其他甲基转移酶表现出广泛的选择性。通过表面等离振子共振实验验证了17与PRMT5的直接结合，K d为0.987μM。动力学实验表明17是除底物以外的SAM竞争性抑制剂。另外17提示对MV4-11细胞具有选择性的抗增殖作用，进一步的研究表明，细胞抗肿瘤活性的机制是由于PRMT5介导的SmD3甲基化的抑制。17可能是一种有前途的先导化合物，可以进一步了解PRMT5，并可能有助于开发白血病适应症的治疗方法。