2-[(2-methyl-1H-benzimidazole-1-yl)methyl]phenol | 776306-49-1

• 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-[(2-methyl-1H-benzimidazole-1-yl)methyl]phenol
• 英文别名: 2-((2-methyl-1H-benzimidazol-1-yl)methyl)phenol；2-[(2-methyl-1H-benzimidazol-1-yl)methyl]phenol；2-[(2-Methylbenzimidazol-1-yl)methyl]phenol
• CAS: 776306-49-1
• 化学式: C₁₅H₁₄N₂O
• 分子量: 238.289
• InChiKey: YWTZDEGPZIURGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(2-methyl-1H-benzimidazole-1-yl)methyl]phenol 、 溴乙酸乙酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 以90%的产率得到ethyl 2-(2-((2-methyl-1H-benzimidazol-1-yl)methyl)phenoxy)acetate
  参考文献：
  名称：

  The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesisin vitroandin vivoby targeting 5-lipoxygenase-activating protein (FLAP)

  摘要：

  Background and PurposeLeukotrienes (LTs) are inflammatory mediators produced via the 5‐lipoxygenase (5‐LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP‐7 as chemotype for anti‐LT agents by virtual screening targeting 5‐LOX‐activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP‐7 as an inhibitor of LT biosynthesis.Experimental ApproachWe analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell‐free assays. The effectiveness of BRP‐7 in vivo was evaluated in rat carrageenan‐induced pleurisy and mouse zymosan‐induced peritonitis.Key ResultsBRP‐7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5‐LOX co‐localization with FLAP. Neither the cellular viability nor the activity of 5‐LOX in cell‐free assays was affected by BRP‐7, indicating that a functional FLAP is needed for BRP‐7 to inhibit LTs, and FLAP bound to BRP‐7 linked to a solid matrix. Compared with the FLAP inhibitor MK‐886, BRP‐7 did not significantly inhibit COX‐1 or microsomal prostaglandin E2 synthase‐1, implying the selectivity of BRP‐7 for FLAP. Finally, BRP‐7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.Conclusions and ImplicationsBRP‐7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti‐inflammatory effectiveness in vivo, with promising potential for further development.

  DOI：

  10.1111/bph.12625
• 作为产物：
  描述：

  2-甲基苯并咪唑 、 水杨醇 以 neat (no solvent) 为溶剂， 反应 0.5h， 以25%的产率得到2-[(2-methyl-1H-benzimidazole-1-yl)methyl]phenol
  参考文献：
  名称：

  包含嘧啶部分的 N-杂环文库的设计、步骤经济多样性导向合成：新型潜在除草剂的发现。

  摘要：

  高度多样化的文库的合成对于获得药物和农用化学品发现的新先导化合物变得至关重要。在此，开发了各种嘧啶-N-杂环杂化物文库的步骤经济的多样性导向合成方法，其中将4,6-二甲氧基嘧啶核心掺入九种N-杂环中。总共 34 种结构不同的化合物是通过两步法从非常简单且市售的起始材料合成的。此外，该文库的体内生物筛选鉴定出 11 种活性化合物，这些化合物在每公顷 750 g ai 剂量下对 D. sanguinalis 表现出良好的芽后除草活性。更重要的是，嘧啶-四氢咔唑杂化物5q在相同剂量下对五种测试杂草表现出良好至优异的除草活性。嘧啶-四氢咔唑杂化物代表了一类新型除草剂，可能成为除草剂发现过程中有前途的先导化合物。

  DOI：

  10.1039/d1ra02663a

文献信息

• Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents
  作者：Dong Ma、Yang Yin、Ying-Lu Chen、Yi-Tao Yan、Jun Wu

  DOI：10.1039/d1ra02663a

  日期：——

  The synthesis of highly diverse libraries has become of paramount importance for obtaining novel leads for drug and agrochemical discovery. Herein, the step-economical diversity-oriented synthesis of a library of various pyrimidine-N-heterocycle hybrids was developed, in which a 4,6-dimethoxypyrimidine core was incorporated into nine kinds of N-heterocycles. A total of 34 structurally diverse compounds

  高度多样化的文库的合成对于获得药物和农用化学品发现的新先导化合物变得至关重要。在此，开发了各种嘧啶-N-杂环杂化物文库的步骤经济的多样性导向合成方法，其中将4,6-二甲氧基嘧啶核心掺入九种N-杂环中。总共 34 种结构不同的化合物是通过两步法从非常简单且市售的起始材料合成的。此外，该文库的体内生物筛选鉴定出 11 种活性化合物，这些化合物在每公顷 750 g ai 剂量下对 D. sanguinalis 表现出良好的芽后除草活性。更重要的是，嘧啶-四氢咔唑杂化物5q在相同剂量下对五种测试杂草表现出良好至优异的除草活性。嘧啶-四氢咔唑杂化物代表了一类新型除草剂，可能成为除草剂发现过程中有前途的先导化合物。
• The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis<i>in vitro</i>and<i>in vivo</i>by targeting 5-lipoxygenase-activating protein (FLAP)
  作者：C Pergola、J Gerstmeier、B Mönch、B Çalışkan、S Luderer、C Weinigel、D Barz、J Maczewsky、S Pace、A Rossi、L Sautebin、E Banoglu、O Werz

  DOI：10.1111/bph.12625

  日期：2014.6

  Background and PurposeLeukotrienes (LTs) are inflammatory mediators produced via the 5‐lipoxygenase (5‐LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP‐7 as chemotype for anti‐LT agents by virtual screening targeting 5‐LOX‐activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP‐7 as an inhibitor of LT biosynthesis.Experimental ApproachWe analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell‐free assays. The effectiveness of BRP‐7 in vivo was evaluated in rat carrageenan‐induced pleurisy and mouse zymosan‐induced peritonitis.Key ResultsBRP‐7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5‐LOX co‐localization with FLAP. Neither the cellular viability nor the activity of 5‐LOX in cell‐free assays was affected by BRP‐7, indicating that a functional FLAP is needed for BRP‐7 to inhibit LTs, and FLAP bound to BRP‐7 linked to a solid matrix. Compared with the FLAP inhibitor MK‐886, BRP‐7 did not significantly inhibit COX‐1 or microsomal prostaglandin E2 synthase‐1, implying the selectivity of BRP‐7 for FLAP. Finally, BRP‐7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels.Conclusions and ImplicationsBRP‐7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti‐inflammatory effectiveness in vivo, with promising potential for further development.