2-(4-isopropylbenzylthio)-5-methoxy-1H-benzo[d]imidazole | 1356959-85-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 2-(4-isopropylbenzylthio)-5-methoxy-1H-benzo[d]imidazole
• 英文别名: 6-methoxy-2-[(4-propan-2-ylphenyl)methylsulfanyl]-1H-benzimidazole
• CAS: 1356959-85-7
• 化学式: C₁₈H₂₀N₂OS
• 分子量: 312.436
• InChiKey: OLVGVEZGCNJPGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  63.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-巯基-5-甲氧基苯并咪唑 、 alkaline earth salt of/the/ methylsulfuric acid 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以85.8%的产率得到2-(4-isopropylbenzylthio)-5-methoxy-1H-benzo[d]imidazole
  参考文献：
  名称：

  Ligand-Based Design of a Potent and Selective Inhibitor of Cytochrome P450 2C19

  摘要：

  A series of omeprazole-based analogues was synthesized and assessed for inhibitory activity against CYP2C19. The data was used to build a CYP2C19 inhibition pharmacophore model for the series. The model was employed to design additional analogues with inhibitory potency against CYP2C19. Upon identifying inhibitors of CYP2C19, ligand-based design shifted to attenuating the rapid clearance observed for many of the inhibitors. While most analogues underwent metabolism on their aliphatic side chain, metabolite identification indicated that for analogues such as compound 30 which contain a heterocycle adjacent to the sulfur moiety, metabolism primarily occurred on the benzimidazole moiety. Compound 30 exhibited improved metabolic stability (Cl-int = 12.4 mL/min/nmol) and was selective in regard to inhibition of CYP2C19-catalyzed (S)-mephenytoin hydroxylation in human liver microsomes. Finally, representative compounds were docked into a homology model of CYP2C19 in an effort to understand the favorable inhibition or metabolism properties.

  DOI：

  10.1021/jm201346g

文献信息

• Design, Synthesis and Antitubercular Activity of 2-(Benzylthio)-1H-benzo[d]imidazoles
  作者：Raoní Rambo、Etienne Waldow、Bruno Abaddi、Maiele Silveira、Adilio Dadda、Nathalia Sperotto、Cristiano Bizarro、Luiz Augusto Basso、Pablo Machado

  DOI：10.21577/0103-5053.20210040

  日期：——

  Using molecular simplification and molecular hybridization approaches, a series of 2-(benzylthio)-1H-benzo[d]imidazoles was synthesized and evaluated as in vitro inhibitors of Mycobacterium tuberculosis (M. tuberculosis) growth. Compounds 6p and 6z were considered the lead compounds from this series of molecules, with minimal inhibitory concentration (MIC) values of 6.9 and 3.8 μM against M. tuberculosis

  利用分子简化和分子杂化方法，合成了一系列2-(苄硫基)-1H-苯并[d]咪唑类化合物，并作为体外抑制结核分枝杆菌(M. tuberculosis)生长的试剂进行评估。该系列化合物中的6p和6z被认为是领先的化合物，对M. tuberculosis H37Rv的最小抑制浓度（MIC）分别为6.9和3.8μM。此外，这些领先的化合物对多药耐药菌株也具有活性，并且对Vero和HepG2细胞没有明显毒性，这是通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物（MTT）和中性红试验得出的。最后，这些化合物具有良好的水溶性和高的血浆稳定性。这些数据表明，这一类分子可能为未来开发新的抗结核病药物候选物提供了可能性。
• US8710082B2
  申请人：——

  公开号：US8710082B2

  公开（公告）日：2014-04-29
• Ligand-Based Design of a Potent and Selective Inhibitor of Cytochrome P450 2C19
  作者：Robert S. Foti、Dan A. Rock、Xiaogang Han、Robert A. Flowers、Larry C. Wienkers、Jan L. Wahlstrom

  DOI：10.1021/jm201346g

  日期：2012.2.9

  A series of omeprazole-based analogues was synthesized and assessed for inhibitory activity against CYP2C19. The data was used to build a CYP2C19 inhibition pharmacophore model for the series. The model was employed to design additional analogues with inhibitory potency against CYP2C19. Upon identifying inhibitors of CYP2C19, ligand-based design shifted to attenuating the rapid clearance observed for many of the inhibitors. While most analogues underwent metabolism on their aliphatic side chain, metabolite identification indicated that for analogues such as compound 30 which contain a heterocycle adjacent to the sulfur moiety, metabolism primarily occurred on the benzimidazole moiety. Compound 30 exhibited improved metabolic stability (Cl-int = 12.4 mL/min/nmol) and was selective in regard to inhibition of CYP2C19-catalyzed (S)-mephenytoin hydroxylation in human liver microsomes. Finally, representative compounds were docked into a homology model of CYP2C19 in an effort to understand the favorable inhibition or metabolism properties.