(3-((1H-benzo[d]imidazol-1-yl)methyl)phenyl)methanamine

• 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-((1H-benzo[d]imidazol-1-yl)methyl)phenyl)methanamine
• 英文别名: {3-[(1H-1,3-benzodiazol-1-yl)methyl]phenyl}methanamine；[3-(benzimidazol-1-ylmethyl)phenyl]methanamine
• 化学式: C₁₅H₁₅N₃
• mdl: MFCD09740095
• 分子量: 237.304
• InChiKey: RCSBTARKNQPCPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-((1H-benzo[d]imidazol-1-yl)methyl)phenyl)methanamine 在 乙酸酐 、 氯化铵 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 13.5h， 生成 N-(2-((3-((1H-benzo[d]imidazol-1-yl)methyl)benzyl)amino)-2-oxoethyl)benzamide
  参考文献：
  名称：

  Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to in Vivo Pharmacodynamic Activity

  摘要：

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.

  DOI：

  10.1021/acs.jmedchem.9b01809
• 作为产物：
  描述：

  3-氰基苄基溴 在 镍 ammonium hydroxide 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 (3-((1H-benzo[d]imidazol-1-yl)methyl)phenyl)methanamine
  参考文献：
  名称：

  A structure–Permeability study of small drug-like molecules

  摘要：

  A systematic structure permeability relationship study on a set of small drug-like molecules with log D values in the range -2.5 to 3 and carrying a diverse Arran of functionality reveals that the compounds with log D>0 and <3 are highly permeable. Surprisingly. several tetrazole derivatives were found to be substrates for efflux pump(s). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01035-1

文献信息

• A structure–Permeability study of small drug-like molecules
  作者：Thomas Fichert、Mehran Yazdanian、John R. Proudfoot

  DOI：10.1016/s0960-894x(02)01035-1

  日期：2003.2

  A systematic structure permeability relationship study on a set of small drug-like molecules with log D values in the range -2.5 to 3 and carrying a diverse Arran of functionality reveals that the compounds with log D>0 and <3 are highly permeable. Surprisingly. several tetrazole derivatives were found to be substrates for efflux pump(s). (C) 2003 Elsevier Science Ltd. All rights reserved.
• Discovery of Highly Potent Benzimidazole Derivatives as Indoleamine 2,3-Dioxygenase-1 (IDO1) Inhibitors: From Structure-Based Virtual Screening to <i>in Vivo</i> Pharmacodynamic Activity
  作者：Marta Serafini、Enza Torre、Silvio Aprile、Erika Del Grosso、Alessandro Gesù、Alessia Griglio、Giorgia Colombo、Cristina Travelli、Salvatore Paiella、Annalisa Adamo、Elena Orecchini、Alice Coletti、Maria Teresa Pallotta、Stefano Ugel、Alberto Massarotti、Tracey Pirali、Silvia Fallarini

  DOI：10.1021/acs.jmedchem.9b01809

  日期：2020.3.26

  In this study, a successful medicinal chemistry campaign that exploited virtual, biophysical, and biological investigations led to the identification of a novel class of IDO1 inhibitors based on a benzimidazole substructure. This family of compounds is endowed with an extensive bonding network in the protein active site, including the interaction with pocket C, a region not commonly exploited by previously reported IDO1 inhibitors. The tight packing of selected compounds within the enzyme contributes to the strong binding interaction with IDO1, to the inhibitory potency at the low nanomolar level in several tumoral settings, and to the selectivity toward IDO1 over TDO and CYPs. Notably, a significant reduction of L-Kyn levels in plasma, together with a potent effect on abrogating immunosuppressive properties of MDSC-like cells isolated from patients affected by pancreatic ductal adenocarcinoma, was observed, pointing to this class of molecules as a valuable template for boosting the antitumor immune system.