3-[(6-methoxy-1H-benzimidazol-2-yl)sulfanyl]propan-1-ol | 1156845-39-4

• 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: 3-[(6-methoxy-1H-benzimidazol-2-yl)sulfanyl]propan-1-ol
• CAS: 1156845-39-4
• 化学式: C₁₁H₁₄N₂O₂S
• mdl: MFCD12177743
• 分子量: 238.31
• InChiKey: FUVYXGUCJOVMNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  83.4
• 氢给体数：
  2
• 氢受体数：
  4

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8.8%的产率得到3-[(6-methoxy-1H-benzimidazol-2-yl)sulfanyl]propan-1-ol
  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

• 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.